Infusion Of Neurotensin Research Articles

Cardiovascular and abdominal motor responses evoked by intravenous neurotensin in guinea pigs

The intravenous (IV) infusion of neurotensin (NT) in anesthetized guinea pigs was found to elicit dose-dependent increases of systemic blood pressure (BP) and of heart rate (HR), accompanied by abdominal motor responses consisting in transient, twitch-like contractions of the abdominal wall (TAWC), and a slowly developing, relatively sustained increase of the basal abdominal wall tension (AWT). The TAWC responses were inhibited in animals pretreated with pancuronium, morphine, clonidine, and CP-96,345 [a neurokinin (NK) antagonist], were potentiated by naloxone, but were not modified by atropine or prior (30 s) intraperitoneal (IP) injection of lidocaine. The BP increases caused by IV NT were reduced by clonidine and by IP lidocaine only. The HR increases were attenuated by morphine and clonidine only. Increases of the basal AWT were resistant to all drug treatments and were atributed to a passive stretch of the abdominal wall caused by cecal distension. No defecation was observed in any of the animals given IV NT. These results were interpreted as an indication that the pressor and TAWC responses to IV NT represent an integrated nociceptive response likely to be triggered in part by NT-induced activation of abdominal visceral afferents. A NK acting through NK-1 receptors may participate in TAWC responses to IV NT.

Intracerebroventricular infusion of neurotensin suppresses gastric acid secretion in dogs.

Synthetic neurotensin (NT) was infused intracerebroventricularly in 14 mongrel dogs to study the effects of the peptide on gastric secretion and on gastrin and NT levels. The infusion was performed with a specific apparatus, and gastric fluid was collected with a Pavlov pouch. NT was given in two series of experiments: as a bolus intracerebroventricular injection of 269.8 pmol/kg and as a continuous intracerebroventricular infusion at a rate of 539.6 pmol/kg/h for 30 min. The bolus injection caused a very significant decrease of gastric fluid volume, a significant decrease of HCl output and a significant increase of its pH, while serum immunoreactive gastrin increased significantly. The continuous infusion of NT caused similar changes in gastric secretion. The plasma NT levels did not change. In conclusion, the intracerebroventricular administration of NT increases the serum gastrin levels, decreases the volume and HCl content of gastric fluid, and increases its pH.

Somatostatin as a mediator of the effect of neurotensin on pentagastrin-stimulated acid secretion in rats

Neurotensin and somatostatin have both been shown to inhibit gastric acid secretion, but no interaction between these peptides has been demonstrated. To determine whether somatostatin might be a mediator of neurotensin's effect on pentagastrin-stimulated gastric acid secretion, we performed the following three experiments. First, we collected 0.2-ml samples of portal venous blood as frequently as every 5 min, and we confirmed a significant release of somatostatin-like immunoreactivity into portal venous blood during neurotensin-induced inhibition of acid secretion. This release of somatostatin-like immunoreactivity and inhibition of acid secretion were only seen in pentobarbital-anesthetized rats, but no sustained release of somatostatin-like immunoreactivity or inhibition of acid secretion occurred in urethane-anesthetized animals. In the second experiment, we analyzed portal plasma by high pressure liquid chromatography, and found that portal somatostatin-like immunoreactivity in blood collected during neurotensin infusion was composed of a single peak corresponding to somatostatin-14. In the third experiment, we found that infusion of antibody to somatostatin prevented neurotensin from inhibiting pentagastrin-stimulated acid secretion. Taken together, these data show that somatostatin, possibly from the stomach itself, is a necessary mediator of neurotensin's inhibitory effect in pentobarbital-anesthetized rats.

Neurotensin increases extracellular striatal dopamine levels in vivo

This study employed intracranial microdialysis to assess the effects of neurotensin (NT) infusion on extracellular dopamine (DA) and DA metabolite concentrations in the rat striatum and nucleus accumbens, and the effects of NT on alterations in extracellular DA levels induced by cocaine and the DA D-2 receptor agonist, quinpirole. Direct NT infusion (.10, 1.0, 10.0 μM) did not significantly affect extracellular DA in the nucleus accumbens, but did produce a significant increase in the DA metabolite homovanillic acid (HVA). In contrast, direct NT infusion produced an increase in striatal DA levels, without altering DA metabolites. Neurotensin infusion (.10 μM) into the striatum significantly attenuated the peak DA increase induced by an intraperitoneal (IP) injection of a low dose (10.0 mg/kg) but not a high dose (30.0 mg/kg) of cocaine. Neurotensin infusion (.10 μM) did not affect the decrease in DA and its metabolites induced by an IP injection of a low dose of quinpirole (.03 mg/kg), but did alter the decrease in HVA induced by a high dose of quinpirole (.10 mg/kg). These results suggest that NT differentially affects in vivo DA release in the striatum and nucleus accumbens, and further strengthens the assertion that NT is an important modulator of dopaminergic function.

Study of the effect of neurotensin on meal- and cerulein-induced gallbladder contraction.

We studied the effect of a low dose of neurotensin (2.5 pmol/kg/min) on meal- and cerulein-induced gallbladder contraction in 11 healthy volunteers by means of real-time ultrasonography. Ingestion of a meal caused a significant reduction in gallbladder volume which reached a maximum of 57 +/- 2% of the basal value at 60 min after the meal. The infusion of neurotensin caused a slight but not significant attenuation of the contractile response of the gallbladder to the meal (maximal reduction of 49 +/- 6%). Increasing doses of cerulein (10, 20 and 40 ng/kg/h, for 30 min at each dose) caused progressive reductions in gallbladder volume of 18 +/- 5, 72 +/- 5 and 89 +/- 4% with the three respective doses of cerulein used. The simultaneous administration of neurotensin did not significantly modify the gallbladder response to cerulein. The results indicate that neurotensin, at a dose of 2.5 pmol/kg/min, does not influence the gallbladder contraction stimulated by food or cerulein.

The role of endogenous prostaglandins in hormone-stimulated pancreatic exocrine secretion

The authors have previously shown that neurotensin and secretin inhibit gastric acid secretion in the dog and that these actions are inhibited by the prostaglandin synthesis inhibitor indomethacin. Conversely, neurotensin and secretin share similar stimulatory effects on pancreatic exocrine secretion. In the present study, the effects of blockade of prostaglandin synthesis by indomethacin on neurotensin-, cholecystokinin-, and secretin-stimulated exocrine secretion are examined along with the effects of these same agents on the release of pancreatic polypeptide. The studies were performed on conscious dogs with chronic gastric and pancreatic cannulas. Dose-dependent increases in pancreatic exocrine secretion of water and bicarbonate were observed with IV infusion of neurotensin or secretin; however, inhibition of prostaglandin synthesis by indomethacin abolished this response. Protein secretion stimulated by either neurotensin or cholecystokinin was not affected by prostaglandin inhibition. Cholecystokinin and neurotensin infusion stimulated release of pancreatic polypeptide; only neurotensin-stimulated release of pancreatic polypeptide was inhibited by indomethacin treatment. It is concluded that intact prostaglandin synthesis is necessary for the actions of neurotensin and secretin (but not that of cholecystokinin) on pancreatic exocrine secretion of water and bicarbonate and for neurotensin- (but not cholecystokinin-) stimulated release of pancreatic polypeptide.

Neuromedin-N inhibits migrating myoelectric complex and induces irregular spiking in the small intestine of rats; comparison with neurotensin

The effects of neuromedin-N on migrating myoelectric complexes in the small intestine of rats were studied. As neuromedin-N and neurotensin are structurally related peptides a comparison with neurotensin was made. Myoelectric activity was recorded by means of three bipolar electrodes implanted into the wall of the small intestine at 5, 15 and 25 cm distal to the pylorus. The peptides were administered as intravenous infusions to fasted conscious rats. Neuromedin-N at doses of 100–800 pmol kg −1 min −1 caused a dose-dependent disruption of the migrating myoelectric complexes and induced irregular spiking activity ( n = 7, P < 0.05). Neurotensin induced a similar response, but at doses of 1.0–8.0 pmol kg −1 min −1 ( n = 5, P < 0.05). Thus, on a molar basis, neuromedin-N appeared to be about 100-times less potent than neurotensin. Hexamethonium (20 mg kg −1 i.v.) inhibited the migrating motor complexes and induced quiescence, but did not block the effect of neuromedin-N at a dose of 800 pmol kg −1 min −1. Atropine (1 mg kg −1 i.v.) and mepyramine (2 mg kg −1 i.v.) did not affect the migrating motor complexes, nor did they block the effect of neuromedin-N. Simultaneous infusion of neuromedin-N and neurotensin in a 1 : 1 molar ratio at doses of 2 pmol kg −1 min −1 showed inhibition of the response to neurotensin in eight out of ten experiments. In conclusion, neuromedin-N changes the myoelectric activity in the small intestine from a fasting to a fed pattern. Neuromedin-N is less potent but exerts similar effects as neurotensin. The mechanism of neuromedin-N action on motility could not be shown to involve cholinergic mechanisms or H 1-receptors, but may involve the same receptors as neurotensin, modulating the effects of this peptide.

Increase of Biliary Excretion of Reverse Triiodothyronine in Rats During the Infusion of Neurotensin Possibly Resulting from the Inhibition of Iodothyronine 5'-Monodeiodination

Male rats weighing about 350 g were inserted polyethylene tubes into the bile duct and femoral vein under pentobarbital anaesthesia. After taking the first (control) 2-h bile sample the control group (n = 24) was infused saline for 4 h and the other group (n = 14) was infused neurotensin in a dose of 27 micrograms per animal per 4 h. The concentration of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in the bile was estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of neurotensin was significantly increased which was not the case in controls. Since neurotensin is known to increase glycemia which effect might be or might not be mediated by glucagon, it may be suggested that these results bring an additional support for the previously reported coincidence between a prevailing effect of gluconeogenetic hormones and inhibition of iodothyronine 5'-deiodination in the liver.

Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin

The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 mug/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthesized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthesizex with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under those conditions in anesthesized rats.

Effects of neurotensin on the pituitary-adrenocortical axis of intact and dexamethasone-suppressed rats

A 7-day infusion with neurotensin (NT) (10 µg · kg-1 · day-1) stimulated adrenal growth in intact female rats, and raised ACTH blood concentration, without altering corticosterone (B) plasma level and output by adrenal homogenates. For a week dexamethasone (Dx) administration (125 µg · kg-1 - day-1) caused a notable adrenal atrophy, a marked lowering of ACTH and B blood concentrations, and a profound depression of B output by adrenal homogenates. NT infusion reversed Dx-induced adrenal atrophy and plasma ACTH-level drop, but not the impairment in adrenal-cortex secretory activity. In vitro studies showed that NT (10-6 mol/1) significantly reduced basal, but not ACTH-stimulated B release by isolated rat inner adrenocortical cells. These findings suggest that NT exerts a direct inhibitory effect on B production by rat adrenals, while it is able to enhance ACTH secretion and consequently adrenal growth. Moreover, they indicate that NT evokes a striking, and at present unexplained dissociation between structure and function in the adrenal cortex of Dx-suppressed rats.

ANTIDIURETIC EFFECTS OF NEUROTENSIN IN CHLORALOSE ANAESTHETIZED DOGS

1. Effects of cerebroventricular and/or intravenous infusions of neurotensin (NT), an endogenous tridecapeptide, on haemodynamics and renal function were investigated in chloralose anaesthetized dogs. 2. Cerebroventricular infusions (i.c.v.) of NT (10-6 mol/L and 10-5 mol/L, 0.1 mL/min) for 30 min did not produce any significant alterations in the measured variables. In the vagotomized dogs, intravenous (i.v.) infusion of NT (10(-5) mol/L) at a rate of 0.1 mL/min for 30 min significantly lowered the arterial blood pressure and glomerular filtration rate; these effects were accompanied by pronounced reductions in the urine flow and urinary sodium excretion and marked increases in urine osmolality. 3. In the dogs with vagi intact, i.v. infusions of NT failed to produce any alterations in the blood pressure; however, renal effects of NT were essentially identical to those observed in the vagotomized dogs. 4. Infusions of NT (10(-6) mol/L) and/or NT-metabolites NT1-8 and NT8-13 (10(-5) mol/L) directly into the renal artery failed to produce any significant alterations in the urine flow. Antidiuretic effects of i.v. NT were not prevented by acute renal denervation, adrenalectomy, or pretreatment of the animals with naloxone. However, morphine pretreatment completely abolished the hypotensive and anti-diuretic effects of NT. 5. It is proposed that i.v. infusion of NT rapidly facilitates the secretion of an endogenous substance possessing potent antidiuretic properties and opiate mechanisms are involved in mediating such an effect. Although it appears unlikely, a role for vasopressin cannot be ruled out.

Inhibitory effect of neurotensin on gastric acid secretion in rats

Neurotensin has been shown to inhibit gastric acid secretion when administered in pharmacological doses, but no information has been available concerning its possible dose-related effect during intravenous infusion. In this study, a dose-related and reversible inhibitory effect of neurotensin was demonstrated in pentobarbital-anesthetized female Sprague-Dawley rats. The rats underwent continuous gastric perfusion with saline, 1 ml/min, and intravenous infusion of both pentagastrin and neurotensin. Inhibition of acid secretion did not depend upon the occurrence of hypotension, and ranged from 35 +/- 7% of maximal acid output at 0.24 nmol/kg/hr to 60 +/- 10% at 7.2 nmol/kg/hr of neurotensin. Blood levels of C-terminal neurotensin-like immunoreactivity were proportional to the dose of peptide infused and were 52 fmol/ml during infusion of 0.24 nmol/kg/hr, a dose that significantly inhibited pentagastrin-induced acid secretion. Thus, a model has been developed to study the effect of neurotensin infusion on acid secretion; the concentration of plasma neurotensin-like immunoreactivity at which inhibition occurs in this model is similar to the concentration reported to occur after a nutrient stimulus.

Do normal plasma neurotensin concentrations increase ileal output?

Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17–36) and 39 (25–43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3–27) and 32 (15–82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82–422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16–108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum.

Pharmacokinetics and metabolism of neurotensin in man.

We studied the pharmacokinetics, arteriovenous extraction, and degradation sites of neurotensin (NT) in man during iv infusions of synthetic intact NT [NT-(1-13)] and the NH2-terminal metabolite NT-(1-8) during lipid ingestion and by catheterization of various vascular beds in normal subjects and patients with hepatic disease. NT-like immunoreactivities in plasma were quantitated using 2 sequence-specific RIAs and gel filtration chromatography. During iv infusion of NT-(1-13) in 6 normal subjects, the median t1/2 was 1.7 min (interquartile range, 0.7-2.8), the MCR was 36 mL/kg.min (range, 21-54), and distribution space was 78.8 mL/kg (range, 56-91). The results were similar at infusion rates of 72, 144, and 288 pmol/kg.h (n = 6). During infusion of NT-(1-8) in 7 normal subjects, the median t1/2 was 8.3 min (range, 4.7-13.8), the MCR was 11.0 mL/kg.min (range, 6.7-21.7), and the distribution space was 142.6 mL/kg (range, 45.3-281.0). Significant peripheral arteriovenous extraction of NT-(1-13) was found at infusion rates of 144 and 288 pmol/kg.h. Extraction of NH2-terminal immunoreactivity was not significant. Intact NT was identified by gel chromatography in arterial plasma after lipid ingestion and iv infusion of NT-(1-13), but postprandially in only low concentrations. In 17 patients with various nonhepatic diseases, plasma intact NT levels were not different in blood sampled from the renal vein, inferior vena cava, brachial artery, or hepatic vein. In contrast, NH2-terminal immunoreactivity was significantly higher in hepatic venous than in systemic plasma. In 6 patients with hepatic disease, systemic plasma intact NT levels were increased, but even more so in hepatic venous plasma. These results demonstrate that metabolism of intact NT is rapid, and a significant peripheral arterio-venous extraction is present. Further studies are necessary to establish if the liver is a site of degradation of intact NT in man.

Effects of intraarterial, intravenous, and intraluminal neurotensin on canine ileal sodium and water absorption and blood flow

Neurotensin is a regulatory peptide which is found primarily in the ileum and is secreted into the blood and lumen. The Physiologic effects of neurotensin are uncertain but in certain pathologic states neurotensin increases to levels which can have effects on many organs. The effects of intravenous, intraarterial and intraluminal neurotensin (0.075–7.5 μg/min) on fed canine ileal sodium and water fluxes, potassium secretion, and blood flows were studied. Intravenous and intraarterial infusion of neurotensin increased net sodium, potassium, and water secretion, due to increased secretory fluxes, and increased hematocrits. Intraarterial neurotensin was not more effective than intravenous neurotensin except for stimulating potassium secretion. Neurotensin increased potassium secretion at 0.075 μg/min IA, increased sodium and water secretion at 0.75 μg/min IA and IV, and increased hematocrit at 7.5 μg/min IA and IV. Total and absorptive site blood flows and arterial and venous pressures were not changed. Intraluminal neurotensin had no effects at any infusion rate. Neurotensin can increase potassium secretion at physiologic levels by a local effect and can increase sodium and water secretion at high physiological-pathological levels through a hormonal mechanism. The secretion is not dependent on cardiovascular changes.

Local effect of neurotensin on canine ileal blood flow, and its release by luminal lipid.

This study was performed to determine whether the level of neurotensin in mesenteric venous blood after lipid perfusion is sufficient to establish neurotensin as a mediator of lipid-induced mesenteric vasodilation. In anesthetized dogs, arterial flow to segments of the ileum was recorded, and blood was collected for measurement of neurotensin-like immunoreactivity, and neurotensin and metabolites. Perfusion of the lumen with micellar lipid resulted in an increase in blood blow from 37.7 +/- 4.1 to 44.5 +/- 3.9 ml/min/100 g (p less than 0.01; n = 8); flow to a control segment did not change. Venous plasma neurotensin-like immunoreactivity doubled, and neurotensin also increased (to 11.3 +/- 3.9 fmol/ml; p less than 0.05). Close intra-arterial infusion of neurotensin at 5 pmol/min increased blood flow to 44.3 +/- 3.4 ml/min/100 g (p less than 0.025; n = 5); flow to a control segment did not change. Neurotensin-like immunoreactivity increased to the same extent as with lipid perfusion, and neurotensin increased to 28.6 +/- 6.1 fmol/ml (p less than 0.05). No accumulation of metabolites was detected in either experiment. Thus, infused neurotensin caused increased ileal blood flow at a level in venous plasma comparable to that present after lipid perfusion, suggesting that neurotensin may have a role in the local regulation of ileal blood flow.

Neurotensin metabolism in the rat: Contribution of the kidney

The kidney plays a key role in the metabolism of neurotensin (NT). We have examined the renal mechanisms of NT clearance by measuring plasma NT basally and after 45 min infusion of NT(1–13) in intact rats, anephric rats (no glomerular filtration, no peritubular metabolism) and ureteral ligated rats (reduced filtration). Plasma NT was measured by radioimmunoassay with both C (biologically active end) and N terminal directed antisera. In anephric and ureteral ligated rats, basal plasma NT like immunoreactivity measured with either antisera was increased 3-fold compared with unoperated rats. C terminal concentrations were higher than N indicating that a C terminal variant of NT was present in basal plasma. Infusion of NT(1–13) increased N terminal NT from 36±3 to 249±35 pmol/l ( p<0.01) in unoperated rats with significantly larger increases in the renally compromised groups. This was reflected in the reduced metabolic clearance rates (measured with the N terminal directed antisera) in the anephric (16±1 ml/kg/min) and ureteral ligated (17±3 ml/kg/min) rats when compared with the control rats (26±4 ml/kg/min). The similar reductions in the anephric and ureteral ligated rats suggested that the decrease in N terminal NT metabolism was from the absence of filtration. Infusion of NT did not increase C terminal NT immunoreactivity in intact, anephric and ureteral ligated rats showing that the C terminal end was extremely labile. However when endogenous converting enzyme activity was blocked by captopril administration there was a significant increase in C terminal immunoreactivity suggesting a role for converting enzyme like proteases in the clearance of the biologically active end of NT. The results indicate that glomerular filtration is important for the clearance of N terminal NT while the C terminal part can be rapidly cleared by non-renal mechanisms. The higher concentration of C than N terminal immunoreactivity in basal plasma of intact rats and the further increase when renal function is reduced suggests that a NT variant sharing the C terminal end may be of physiological significance.

Participation of capsaicin-sensitive neurons in the cardiovascular effects of neurotensin in guinea pigs

Intravenous (IV) infusions of neurotensin (NT) in anesthetized guinea pigs elicited dose-dependent pressor effects and tachycardia. Both effects were significantly reduced or abolished in guinea pigs given a chronic treatment with the neurotoxin capsaicin. In guinea pig isolated atria NT evoked a positive inotropic and chronotropic effect. Both effects were completely abolished in atria derived from capsaicin-treated guinea pigs. The positive inotropic and chronotropic effects of NT in guinea pig atria were mimicked by capsaicin and calcitonin gene-related peptide (CGRP). These results were interpreted as an indication that NT produces its cardiovascular effects in guinea pigs by activating capsaicin-sensitive sensory neurons.

Regulation of gastric acid secretion by neurotensin in man. Evidence against a hormonal role.

The present study was designed to evaluate neurotensin as a hormonal regulator of gastric acid secretion in man. After a fat-rich meal, the strongest known stimulus of neurotensin release, plasma neurotensin-like immunoreactivity (NTLI) was elevated from 7.6 +/- 1.9 to 15.5 +/- 2.5 pM. Plasma NTLI was measured with antiserum L170, which requires the biologically active carboxyl-terminal hexapeptide of the neurotensin molecule for recognition and does not crossreact significantly with any known natural catabolite in human plasma. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 resulted in a plasma level of 14.7 +/- 2.1 pM, similar to the maximal physiological level observed after the fat-rich meal. Intravenous infusion of neurotensin at 25 pmol X kg-1 h-1 during 2 h, however, failed to significantly inhibit peptone meal-stimulated gastric acid secretion measured by intragastric titration. The 2-h acid output to peptone was 40.8 +/- 6.2 and 41.3 +/- 6.9 mmol during the vehicle and the neurotensin infusion, respectively. Intravenous infusion of neurotensin at 100 or 400 pmol X kg-1 h-1 did not affect acid output, whereas at 1,600 pmol X kg-1 h-1, which resulted in a plasma neurotensin concentration of 725 +/- 80 pM, significantly reduced peptone meal-stimulated gastric acid secretion. The neurotensin-induced inhibition of acid output was independent of the hormone gastrin. The present results provide evidence against a hormonal role for neurotensin in the regulation of meal-stimulated gastric acid secretion in man.

Renal function during bovine neurotensin infusion in man

The peptide hormone neurotensin (NT) is found mainly in gut endocrine cells of the ileum, but has also been identified as a putative neurotransmitter in the central and peripheral nervous systems. It may have a dual role as a circulating gastrointestinal hormone and peripheral neurotransmitter. Its predominant effects are to reduce oesophageal sphincter tone, inhibit gastric secretion and emptying and inhibit intestinal motility, but stimulate intestinal and pancreatic exocrine secretion; NT-like immunoreactivity has been found in kidney and therefore NT may influence renal function. When infused i.v. in rabbits it causes antinatriuresis. We have studied its renal effects in 11 healthy males by i.v. infusion under conditions of altered dietary sodium. Postprandial circulating neurotensin levels were reproduced by infusion. There were no consistent systemic or renal haemodynamic effects. Plasma electrolytes and renin did not change. Only renal chloride excretion changed significantly, falling by ca. 30%, and recovering after infusion. There is no evidence for a specific renal tubular chloride transport mechanism, but coupled cotransport, Na +:K +:2Cl −, may be hormonally regulated. NT might stimulate this process and contribute to the renal response to changes in dietary composition, especially sodium intake.